The major objectives of this study are to a) further characterize amino acid, glucose and potassium transport in normal and leukemic leukocytes, b) to examine the responses of such transport systems to environmental alterations in amino acids, glucose, and potassium, c) to examine the responses of these cell membrane functions to hormones and chemotherapeutic agents in vitro and in vivo and d) to correlate therapeutic responsivity with drug sensitivity of transport systems when treatment is warranted on clinical grounds. We plan to characterize more completely substrate transport in lymphocytes and myeloblasts using our highly reproducible techniques for measurement of cellular radiolabelled amino acid, sugar, and potassium accumulation. We further plan to examine the effect of hormones and chemotherapeutic agents in vitro and in vivo of the time-related (adaptive) response of cells in order to study whether chemotherapeutic effects are correlated with impairment of either the steady-state or the adaptive acceleration in membrane transport rates. Preliminary studies indicate that the adaptive increase in amino acid transport which occurs in vitro if substrate concentration is reduced is lost if cells are treated with a chemotherapeutic agent to which they are sensitive, whereas adaptation is not lost if the cells are insensitive to the chemotherapeutic agent or hormone. Hence, it may be possible to employ amino acid transport as a reliable index of the sensitivity of leukemic leukocytes to chemical agents. These studies may enhance our understanding of nutrient (substrate) acquisition by leukemic cells and the modification of these processes by hormones and drugs, and lead to the development of a new method for predicting therapeutic efficacy. Also, our studies should enhance understanding of leukemic cell substrate acquisition and of the modification of such processes by drugs. BIBLIOGRAPHIC REFERENCES: Brennan, J.K., Lichtman, M.A., Chamberlain, J.K. and Leblond, P. Isolation of a variant lymphoma cell with reduced growth requirements for extracellular calcium and magnesium and enhanced oncogenicity. Blood 47: 447, 1976. Segel, G.B., Gordon, B.R., Lichtman, M.A., Hollander, M.M. and Klemperer, M.R. Exodus of 42K and 86Rb from rat thymic and human blood lymphocytes exposed to phytohemagglutinin. J. Cell. Physiol. 87: 337, 1976.